There is increasing evidence that the development of noninsulin dependent diabetes mellitus (NIDDM) is presaged many years earlier by the presence of biochemical and other phenotypic features in susceptible individuals. Earlier intervention in such individuals may prevent or slow the occurrence of overt hyperglycemia which, in turn, may limit the morbidity and mortality associated with diabetes. By selecting populations at higher than average risk for the ultimate development of NIDDM, we propose to be able to practically test the following hypothesis: The reduction in risk of developing NIDDM in persons at high risk for the development of diabetes will be dependent on treatment which affects insulin resistance, islet B-cell dysfunction, and/or hepatic glucose production. Interventions which include diet, exercise sulfonylurea drugs, and metformin in a factorial design can address this hypothesis. The Diabetes Center at the Albert Einstein College of Medicine is a multidisciplinary aggregation of scientists and clinicians actively involved in various aspects of diabetes. With the resources and expertise available among individuals in the Center, we will participate in a multicenter NIDDM Prevention Trial. The Albert Einstein Center would be able to contribute to the success of such a Trial for the following reasons: l) a Diabetes Research and Training Center underpinning and the Institutional commitment to addressing issues in underserved populations of New York City; 2) our participation in the Diabetes Control and Complications Trial as a clinical center; 3) the availability of a large, identified population of individuals from racial and ethnic minority groups in the Bronx and Westchester Counties who receive their medical care in Einstein-affiliated programs; 4) an identified and well characterized population of women who had gestational diabetes diagnosed between 1988 and the present, and an annual accrual of an additional cohort of women with gestational diabetes; 5) expertise in the design and implementation of clinical trials; 6) strong research foci of the principal and co-investigators in areas such as pathophysiology and diagnosis as well as nutritional and pharmacologic treatment of NIDDM; 7) members of the treatment team with specific competence in diabetes in Hispanic and in African-American individuals; 8) a new outpatient facility in which to conduct a clinical trial; 9) expertise in related areas such as hypertension control, cardiovascular risk reduction, and behavioral techniques intended to achieve therapeutic goals; and lO) a track record of participating in constructive collaborative efforts to achieve the goals of NIH-initiated multicenter projects. We will participate in the Trial by providing personnel, resources, and study volunteers to achieve the aims of the planning, implementation, and data analysis phases of the proposed 7-year study.